Supplemental Figures (revised) from MACC1 Induces Tumor Progression in Transgenic Mice and Colorectal Cancer Patients via Increased Pluripotency Markers Nanog and Oct4

Lemos, Clara; Hardt, Markus S.; Juneja, Manisha; Voss, Cynthia; Förster, Susann; Jerchow, Boris; Haider, Wolfram; Bläker, Hendrik; Stein, Ulrike

doi:10.1158/1078-0432.22457528.v1

Supplemental Figures (revised) from MACC1 Induces Tumor Progression in Transgenic Mice and Colorectal Cancer Patients via Increased Pluripotency Markers Nanog and Oct4

https://doi.org/10.1158/1078-0432.22457528

journal contribution

posted on 2023-03-31, 18:28 authored by Clara Lemos, Markus S. Hardt, Manisha Juneja, Cynthia Voss, Susann Förster, Boris Jerchow, Wolfram Haider, Hendrik Bläker, Ulrike Stein

<p>Supplementary Figure 1. Generation of transgenic mice with IEC-specific overexpression of MACC1. Supplementary Figure 2. Characterization of the vil-MACC1 transgenic mice Supplementary Figure 3. MACC1 transgene expression in the vil-MACC1/ApcMin mice. Supplementary Figure 4. Characterization of the vil-MACC1/ApcMin mice. Supplementary Figure 5. Pathway analysis of the Affymetrix microarray.</p>

Funding

Alexander von Humboldt Foundation

Wilhelm Sander Foundation

Monika-Kutzner foundation

German Cancer Consortium

Preclinical Comprehensive Cancer Center

History

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DOI - Is supplement to MACC1 Induces Tumor Progression in Transgenic Mice and Colorectal Cancer Patients via Increased Pluripotency Markers Nanog and Oct4

ARTICLE ABSTRACT

Purpose: We have previously identified the gene MACC1 as a strong prognostic biomarker for colorectal cancer metastasis and patient survival. Here, we report for the first time the generation of transgenic mouse models for MACC1.Experimental Design: We generated mice with transgenic overexpression of MACC1 in the intestine driven by the villin promoter (vil-MACC1) and crossed them with ApcMin mice (vil-MACC1/ApcMin).Results: vil-MACC1/ApcMin mice significantly increased the total number of tumors (P = 0.0056). This was particularly apparent in large tumors (≥3-mm diameter; P = 0.0024). A detailed histopathologic analysis of these lesions demonstrated that the tumors from the vil-MACC1/ApcMin mice had a more invasive phenotype and, consequently, showed a significantly reduced survival time than ApcMin mice (P = 0.03). Molecular analysis revealed an increased Wnt and pluripotency signaling in the tumors of vil-MACC1/ApcMin mice. Specifically, we observed a prominent upregulation of the pluripotency markers Oct4 and Nanog in these tumors compared with ApcMin controls. Finally, we could also validate that Oct4 and Nanog are regulated by MACC1 in vitro and strongly correlate with MACC1 levels in a cohort of 60 tumors of colorectal cancer patients (r = 0.7005 and r = 0.6808, respectively; P > 0.0001 and P > 0.0002, respectively).Conclusions: We provide proof of principle that MACC1-induced tumor progression in colorectal cancer acts, at least in part, via the newly discovered MACC1/Nanog/Oct4 axis. These findings might have important implications for the design of novel therapeutic intervention strategies to restrict tumor progression. Clin Cancer Res; 22(11); 2812–24. ©2016 AACR.